Macrophages Infiltration In Low Grade Glioma And Its Value In Prognosis Prediction

PurposeObjective to detect the infiltration degree and functional state of tumor-associated macrophages（TAM）in different low-grade glioma（LGG）subtypes,and to analyze the value of TAM related biomarkers in predicting LGG patients’prognosis.MethodsWe downloaded 529 LGG data from The Cancer Genome Atlas（TCGA）,and compared the expression levels of TAM infiltration biomarkers between IDH1/2-wt LGG and IDH1/2-mu LGG.Then we analyzed the value of CD163 and IL-10 in predicting LGG patients’prognosis.We also detected the infiltration degree of TAM by using immunohistochemical staining in 17 IDH1/2-wt and 19 IDH1/2-mu LGG clinical samples.Mann-Whitney U test,COX regression and Kaplan-Meier method were used for statistical analysis.ResultsTCGA data analysis showed that the expression of macrophages and TAM markers CD11b（Mann-Whitney U=15836,P<0.01）、CD68（Mann-Whitney U=19425,P=0.01）、IBA1（Mann-Whitney U=17758,P<0.01）、CD163（Mann-Whitney U=18112,P<0.01）、CD204（Mann-Whitney U=12676,P<0.01）in IDH1/2-mu LGG were significantly less than IDH1/2-wt LGG.Meanwhile,the infiltration degree of TAM in IDH1/2-mu LGG clinical glioma tissues was lower comparing with IDH1/2-wt LGG（Mann-Whitney U=20,P<0.01;Mann-Whitney U=35,P<0.01;Mann-Whitney U=51,P<0.01）.The expression levels of TAM chemokines CCL2（Mann-Whitney U=15841,P<0.01）、CCL5（Mann-Whitney U=11326,P<0.01）、POSTN（Mann-Whitney U=8893,P<0.01）、VEGF-A（Mann-Whitney U=14433,P<0.01）、Neurotensin（Mann-Whitney U=15556,P<0.01）in IDH1/2-wt LGG were significantly higher than IDH1/2-mu LGG.Additionally,the expression levels of IL-10（Mann-Whitney U=17334,P<0.01）and TGF-β（Mann-Whitney U=15459,P<0.01）produced by TAM were significantly up-regulated in IDH1/2-wt LGG.Furthermore,survival analysis showed that in IDH1/2-wt group,the overall survival rate of CD163^highigh patients was lower than CD163^low patients（P=0.01）,and the overall survival rate of IL-10^high was lower than IL-10^low in IDH1/2-mu LGG patients（P<0.05）.ConclusionThe infiltration numbers of TAM and immunosuppression states are significantly different between IDH1/2-wt LGG and IDH1/2-mu LGG.The expression level of CD163is negatively correlated with prognosis of IDH1/2-wt LGG patients,and the expression level of IL-10 is negatively correlated with prognosis of IDH1/2-mu LGG patients...